Abstract
Diabetic nephropathy (DN) is an important public health concern of increasing proportions and the leading cause of end-stage renal disease (ESRD) in diabetic patients. It is one of the most common long-term microvascular complications of diabetes mellitus that is characterized by proteinuria and glomerular structural changes. Angiogenesis has long been considered to contribute to the pathogenesis of DN, whereas the molecular mechanisms of which are barely known. Angiogenic factors associated with angiogenesis are the major candidates to explain the microvascular and pathologic finds of DN. Vascular endothelial growth factor A (VEGF-A), leucine-rich α-2-glycoprotein 1, angiopoietins and vasohibin family signal between the podocytes, endothelium, and mesangium have important roles in the maintenance of renal functions. An appropriate amount of VEGF-A is beneficial to maintaining glomerular structure, while excessive VEGF-A can lead to abnormal angiogenesis. LRG1 is a novel pro-angiogenic factors involved in the abnormal angiogenesis and renal fibrosis in DN. The imbalance of Ang1/Ang2 ratio has a role in leading to glomerular disease. Vasohibin-2 is recently shown to be in diabetes-induced glomerular alterations. This review will focus on current understanding of these angiogenic factors in angiogenesis and pathogenesis associated with the development of DN, with the aim of evaluating the potential of anti-angiogenesis therapy in patients with DN.
Highlights
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) in developed countries (Fu et al, 2018)
Abnormal angiogenesis represented by excessive blood vessel formation around glomeruli and increased permeability is associated with glomerular hypertrophy and proteinuria in DN (Osterby and Nyberg, 1987)
Current studies have revealed that Vascular endothelial growth factor A (VEGF-A) and Leucine-richα-2-glycoprotein 1 (LRG1) are important mediators that are involved in the abnormal angiogenesis of DN by promoting glomerular angiogenesis
Summary
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) in developed countries (Fu et al, 2018). Therapies for DN include intensive blood glucose control, as well as blood pressure control by inhibition of renin–angiotensin–aldosterone system (Kato and Natarajan, 2019) These therapeutic strategies only provide limited renal protective effects in preventing DN progressing to ESRD. Angiogenesis is a complex physiological process that involves the interaction between many angiogenic growth factors and endothelium and extracellular matrix (Ucuzian et al, 2010). It requires endothelial cell (EC) proliferation, survival, migration, morphology changes, anastomoses, and extracellular matrix degeneration (Negri et al, 2020). We summarize how these angiogenic factors mediate abnormal angiogenesis associated with DN, with the aim of evaluating their potential in developing innovative therapeutic strategies
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